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Updated: Jul 17, 2026
Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
Microglia in gemistocytic astrocytomas
Fatemeh Geranmayeh1, Bernd W Scheithauer, Christoph Spitzer
1University Department of Neuropathology, Imperial College London, Faculty of Medicine, Division of Neuroscience and Mental Health, Hammersmith Hospitals Trust, London, England.
Objective:
Although gemistocytic astrocytomas are graded as World Health Organization II astrocytomas, they behave more aggressively than other astrocytomas. Their proliferative potential is low, and it remains an intriguing question why these tumors are so biologically "successful." They show a high mutation rate of the P53 gene, cytological abnormalities, and frequent perivascular mononuclear infiltrates. Microglial cells, a feature of this astrocytoma variant, are of increasing interest in the context of glioma growth.
Methods:
We selected 23 tumor biopsies from 201 samples obtained from patients with gemistocytic astrocytomas operated at Mayo Clinic between 1985 and 1998. These tumors were formerly analyzed for P53 mutations, p53 protein, and proliferative activity (). Immunolabeling for three microglial markers, including CR3/43, Ki-M1P, and iba1, was performed on adjacent tissue sections. In addition, in situ hybridization for the alpha-chain of the major histocompatibility complex (MHC) Class II molecule recognized by the CR3/43 monoclonal antibody was performed.
Results:
A high number of microglia was detected in gemistocytic astrocytomas. More microglia were present if the fraction of gemistocytic tumor cells was high (correlation coefficient = 0.699; P < 0.0002). Interestingly, a number of gemistocytes were immunoreactive for MHC Class II molecules, an observation confirmed by in situ hybridization. Importantly, the higher the number of Class II immunoreactive gemistocytes, the fewer Class II positive microglial cells could be detected (correlation coefficient = -0.5649; P < 0.005).
Conclusion:
Our results support the view that gemistocytic astrocytomas contain unusually high numbers of microglial cells. We propose that the finding of aberrant MHC Class II expression by gemistocytic tumor cells correlates with a loss of immune-competent MHC Class II-expressing microglia. This may be related to the especially poor prognosis of gemistocytic astrocytomas for which induction of T cell anergy could provide one explanation.
Insights
Gemistocytic astrocytomas have many microglial cells. Aberrant MHC Class II expression by tumor cells correlates with fewer immune-active microglia, potentially explaining their poor prognosis.
Area of Science:
- Neuro-oncology
- Immunology
- Tumor Biology
Background:
- Gemistocytic astrocytomas (WHO II) exhibit aggressive behavior despite low proliferation.
- These tumors show high P53 mutation rates, cytological abnormalities, and mononuclear infiltrates.
- Microglial cells are increasingly recognized for their role in glioma progression.
Purpose of the Study:
- To investigate the presence and role of microglial cells in gemistocytic astrocytomas.
- To explore the relationship between microglial cells, tumor cells, and major histocompatibility complex (MHC) Class II expression.
Main Methods:
- Analysis of 23 gemistocytic astrocytoma biopsies.
- Immunolabeling for microglial markers (CR3/43, Ki-M1P, iba1).
- In situ hybridization for MHC Class II alpha-chain expression on tumor cells.
Main Results:
- Gemistocytic astrocytomas exhibit a high density of microglial cells.
- Microglia numbers positively correlated with the fraction of gemistocytic tumor cells.
- Gemistocytic tumor cells showed aberrant MHC Class II expression, inversely correlating with the number of MHC Class II-positive microglia.
Conclusions:
- Gemistocytic astrocytomas harbor a significant number of microglial cells.
- Aberrant MHC Class II expression by gemistocytic cells may lead to a loss of immune-competent microglia.
- This immune dysregulation could contribute to the poor prognosis associated with gemistocytic astrocytomas, possibly via T cell anergy induction.
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